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Steriade C, Bauer J, Bien CG. Autoimmune encephalitis-associated epilepsy. Nat Rev Neurol 2025:10.1038/s41582-025-01089-4. [PMID: 40316743 DOI: 10.1038/s41582-025-01089-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2025] [Indexed: 05/04/2025]
Abstract
Autoimmune encephalitis (AE), defined by clinical criteria and its frequent association with neural autoantibodies, often manifests with seizures, which usually stop with immunotherapy. However, a subset of encephalitic conditions present with recurrent seizures that are resistant to immunotherapy. Three primary neurological constellations that fall within this subset are discussed in this Perspective: temporal lobe epilepsy with antibodies against glutamic acid decarboxylase, epilepsy in the context of high-risk paraneoplastic antibodies, and epilepsy following adequately treated surface antibody-mediated AE. These entities all share a common mechanism of structural injury and potentially epileptogenic focal neural loss, often induced by cytotoxic T cells. Recently, we have proposed conceptualizing these conditions under the term autoimmune encephalitis-associated epilepsy (AEAE). Here, we discuss the new concept of AEAE as an emerging field of study. We consider the clinical characteristics of patients who should be investigated for AEAE and highlight the need for judicious use of traditional epilepsy therapeutics alongside immunotherapeutic considerations that are of uncertain and incomplete efficacy for this group of disorders. Last, we discuss future efforts needed to diagnose individuals before structural epileptogenesis has superseded inflammation and to develop improved therapeutics that target the specific immunological or functional disturbances in this entity.
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Affiliation(s)
- Claude Steriade
- New York University Comprehensive Epilepsy Center, New York, NY, USA.
- NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA.
| | - Jan Bauer
- Medical University of Vienna, Vienna, Austria
| | - Christian G Bien
- Dept. of Epileptology, Krankenhaus Mara, Bethel Epilepsy Center, Medical School OWL, Bielefeld University, Bielefeld, Germany
- Laboratory Krone, Bad Salzuflen, Germany
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2
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Dredla BK, Braley TJ. Neuroimmunology and Sleep. Semin Neurol 2025. [PMID: 40209761 DOI: 10.1055/a-2559-7565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2025]
Abstract
The immune system and sleep are inextricably linked in both health and pathological conditions. Tightly regulated neuroimmune processes are critical for the physiological maintenance of healthy sleep. Reciprocally, sleep disturbances can detrimentally affect immune homeostasis and predispose to increased risk of autoimmune conditions, which themselves are bidirectionally associated with a higher risk of sleep disturbances. Autoimmune diseases of the central nervous system (CNS), particularly conditions that affect neuroanatomical regions involved in sleep homeostasis and nocturnal respiration, are associated with an increased risk sleep disorders that may impact diagnosis, clinical course, and management. This review summarizes the bidirectional relationship between sleep and immunity and highlights several exemplar autoimmune conditions of the CNS that include sleep disorders as a consequence or diagnostic feature of the disorder.
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Affiliation(s)
- Brynn K Dredla
- Department of Neurology, and Sleep Disorders Center, Mayo Clinic College of Medicine, Jacksonville, Florida
| | - Tiffany J Braley
- Divisions of Neuroimmunology and Sleep Medicine, Department of Neurology, University of Michigan, Ann Arbor, Michigan
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Sun L, Hu Y, Yang J, Chen L, Wang Y, Liu W, Hong JS, Lv Y, Yang L, Wang Y. Electroencephalographic biomarkers of antibody-mediated autoimmune encephalitis. Front Neurol 2025; 16:1510722. [PMID: 40206289 PMCID: PMC11981172 DOI: 10.3389/fneur.2025.1510722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/28/2025] [Indexed: 04/11/2025] Open
Abstract
Objective To identify electroencephalographic (EEG) biomarkers for different subtypes of antibody-mediated autoimmune encephalitis (AE) and assess their significance in disease severity, treatment response, and prognosis. Methods The clinical and EEG data from 60 AE patients were analyzed. The relationship between EEG severity in the acute phase and disease severity, treatment response, and prognosis was examined to identify factors contributing to poor outcomes. Results The cohort included 60 patients with the following subtypes of encephalitis: anti-LGI1 (22), anti-NMDAR (12), anti-GABABR (7), anti-GAD65 (6), anti-MOG (7), anti-Caspr2 (4), and GFAP-A (2). EEG abnormalities were detected in 96.7% of patients, higher than imaging abnormalities (66.7%, p < 0.05). Common EEG features included focal (86.7%) or diffuse (13.3%) slow waves, interictal epileptiform discharges (IEDs) in temporal (46.7%) or extratemporal (15%) regions, and clinical or subclinical seizures (36.7%). During the recovery phase, 92.6% of 27 patients showed significant improvement in EEG patterns, with reduced slow waves and IEDs. Specific EEG patterns were associated with different antibody subtypes. Anti-LGI1 encephalitis had two clinical-electroencephalographic patterns: one was MTLE-like seizure with ictal activity originating from the temporal region; the other was FBDS with ictal EEG showing generalized electro-decremental activity before or at the onset of seizure with extensive infra-slow activity superimposed with EMG artifacts. Anti-NMDAR encephalitis was marked by abnormal background activity, including extreme delta brush, frontotemporal delta activity, diffuse or focal slow waves, with scattered and unfixed IEDs. MOG antibody cortical encephalitis usually presented as diffuse or focal slow waves in unilateral or bilateral hemisphere accompanied by ipsilateral IEDs, sometimes with periodic lateralized epileptiform discharges (PLEDs). Anti-GABABR and anti-GAD65 encephalitis usually exhibited slow waves, IEDs and ictal activity involving the temporal regions. The EEG severity grading correlated positively with disease severity (r = 0.547, p < 0.0001) and prognosis score (r = 0.521, p < 0.0001). Further ROC curve and binary logistics regression analysis showed moderate to severe abnormal EEG was a risk factor for poor prognosis (OR = 11.942, p < 0.05), with an AUC of 0.756. Conclusion EEG is a sensitive and valuable tool for AE and exhibit common and specific features across different AE subtypes. The severity of EEG abnormalities is a strong predictor of disease outcome.
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Affiliation(s)
- Lu Sun
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Yaping Hu
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Jingjing Yang
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Lihong Chen
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Ying Wang
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Wei Liu
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Jau-Shyong Hong
- Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health, Sciences, Research Triangle Park, Durham, NC, United States
| | - Yunhui Lv
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Lin Yang
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
| | - Ying Wang
- Department of Neurology, The First Affiliated Hospital of DaLian Medical University, Da Lian, China
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Kosek S, Kilsved E, Danfors T, Cunningham JL, Pavel R, Rostedt Punga A, Burman J, Fällmar D. Regional Metabolic Abnormalities in Autoimmune Encephalitis: A Meta-analysis of 498 Cases With Brain FDG PET. Clin Nucl Med 2025; 50:208-213. [PMID: 39601059 DOI: 10.1097/rlu.0000000000005574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
PURPOSE Autoimmune encephalitis (AIE) is a group of conditions that are insufficiently understood and difficult to diagnose. Several publications indicate that FDG PET has superior sensitivity compared with MRI. This study aimed to perform a systematic review of publications to assess the characteristics and frequency of brain FDG PET compared with MRI findings at the individual level in AIE, including case reports and case series. The resulting meta-analysis is complementary to previous publications with large or medium-sized cohorts. PATIENTS AND METHODS The review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and aimed to identify all studies with at least 1 case of AIE in which brain FDG PET was performed. Results from MRI and FDG PET were extracted on a patient-by-patient basis. RESULTS The literature search yielded 1303 results, of which 234 studies were included, containing 498 cases. Abnormal FDG PET findings are reported in 93% compared with 55% with MRI. The affected brain regions, rates of unilateral versus bilateral findings, and hypermetabolism versus hypometabolism are descriptively presented in tables categorized according to the associated antibody. CONCLUSIONS FDG PET detected abnormalities more frequently than MRI, particularly in cases with anti-NMDAR and anti-GABA-B antibodies. Findings include a high prevalence of hypermetabolism in the medial temporal lobes, but also a high prevalence of parietal and occipital hypometabolism. Results differed depending on the associated antibody. Overall, the findings strengthen the importance of FDG PET in patients with suspected AIE, and the antibody-related patterns of regional metabolic abnormalities indicate a high potential for further development as a diagnostic and prognostic tool.
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Affiliation(s)
| | - Ellen Kilsved
- Department of Surgical Sciences, Neuroradiology, Uppsala University, Uppsala, Sweden
| | - Torsten Danfors
- Department of Surgical Sciences, Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden
| | - Janet L Cunningham
- Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Radu Pavel
- Department of Surgical Sciences, Neuroradiology, Uppsala University, Uppsala, Sweden
| | - Anna Rostedt Punga
- From the Department of Medical Sciences, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden
| | - Joachim Burman
- Department of Medical Sciences, Translational Neurology, Uppsala University, Uppsala, Sweden
| | - David Fällmar
- Department of Surgical Sciences, Neuroradiology, Uppsala University, Uppsala, Sweden
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Ketranji O, Alawneh I, Alenizi A, Nigro E, Zimmer MS, Paiz F, Gonorazky H. Neuromyotonia in a 16-year-old female with dramatic improvement after IVIG therapy: Case report and literature review. Neuromuscul Disord 2025; 46:105239. [PMID: 39566368 DOI: 10.1016/j.nmd.2024.105239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/22/2024]
Abstract
Neuromyotonia, also known as Isaac syndrome, is a rare neurological disorder characterized by continuous muscle activity, stiffness, and spontaneous muscle contractions, it is very rare in children. We report a 16-year-old female patient with neuromyotonia. She presented with pain, stiffness, autonomic symptoms and muscle myokymia in both lower limbs. The patient was treated with a short course of methylprednisolone, IVIG over the course of 4 weeks, and symptomatic management which resulted in a dramatic improvement and relief of symptoms. A literature review for pediatric patients with neuromyotonia was conducted revealing 10 reported cases so far. All pediatric patients with neuromyotonia showed favorable prognosis despite using different treatment modalities. Although the association between neuromyotonia and malignancy is known in adult population, this has not been seen in the reported pediatric cases. Indeed, given the scarcity of data, we still do recommend screening for malignancy in pediatric patients with neuromyotonia.
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Affiliation(s)
- Omar Ketranji
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Issa Alawneh
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Asmaa Alenizi
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Elisa Nigro
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Michal S Zimmer
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Freddy Paiz
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Hernan Gonorazky
- Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
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Michelucci R, Pasini E, Riguzzi P, Tappatà M, Giannoccaro MP, Micalizzi E, Lechiara A, Mattioli P, Benedetti L, Villani F. CASPR2-related epilepsy: A distinctive and unrecognized form of epilepsy in adult and elderly males. Epileptic Disord 2024; 26:753-760. [PMID: 39688843 DOI: 10.1002/epd2.20269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/03/2024] [Accepted: 07/30/2024] [Indexed: 12/18/2024]
Abstract
OBJECTIVE The aim of this study was to describe the clinical features of contactin-associated protein-like 2 (CASPR2)-IgG-associated seizures. METHODS Nine patients were retrospectively collected from two epilepsy centers. For each patient we obtained a full clinical, neurophysiological, and MRI study along with detection of antineuronal autoantibodies from serum and CSF. The patients were followed up for 1-6 years. RESULTS The patients were nine male subjects aged 56-85 years (mean: 66) with a 1- to 14-year (mean: 6,3 median: 6) history of seizures. The seizures were classified as focal onset seizures with impaired awareness, usually preceded by epigastric aura (two), piloerection (two), olfactory hallucinations (two), nausea and dizziness (one). Tonic-clonic seizures were present in five patients. Seizure frequency was high in six cases and sporadic in three. Most patients reported memory impairment (eight) or behavioral/mood changes (four). Interictal EEGs usually showed bilateral or unilateral temporal epileptiform abnormalities. A number of seizures arising from the temporal lobes, with bilateral asynchronous onset, were recorded on long-term video-EEG monitoring in two patients. MRI disclosed nonspecific white matter T2 hyperintensities suggestive of chronic vascular changes in four patients and bilateral T2-FLAIR amygdalo-hippocampal hyperintensity in three cases. Neuropsychological study demonstrated various degrees of cognitive impairment in the majority of cases. Increased titers of CASPR2 autoantibodies were detected in the serum and CSF, which persisted over time in four cases. Drug resistance to common anti-seizure medications was present in seven cases who benefited from immunotherapy. SIGNIFICANCE CASPR2-IgG testing should be performed among old male patients with a recent or even not recent onset of focal seizures with impaired awareness particularly when these seizures are accompanied by cognitive impairment or behavioral disturbances. In these cases, anti-seizure medications may be ineffective while immunotherapy may lead to a prompt improvement of seizures and cognitive deficits.
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Affiliation(s)
- Roberto Michelucci
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurology, Bellaria Hospital, Bologna, Italy
| | - Elena Pasini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurology, Bellaria Hospital, Bologna, Italy
| | - Patrizia Riguzzi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurology, Bellaria Hospital, Bologna, Italy
| | - Maria Tappatà
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurology, Bellaria Hospital, Bologna, Italy
| | - Maria Pia Giannoccaro
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Neurological Clinic, Bellaria Hospital, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Elisa Micalizzi
- IRCCS Ospedale Policlinico San Martino, Division of Clinical Neurophysiology and Epilepsy Center, Genoa, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Anastasia Lechiara
- IRCCS Ospedale Policlinico San Martino, Neurological Clinic, Genoa, Italy
| | - Pietro Mattioli
- IRCCS Ospedale Policlinico San Martino, Division of Clinical Neurophysiology and Epilepsy Center, Genoa, Italy
- Department of Neuroscience (DINOGMI), University of Genova, Genoa, Italy
| | - Luana Benedetti
- IRCCS Ospedale Policlinico San Martino, Neurological Clinic, Genoa, Italy
| | - Flavio Villani
- IRCCS Ospedale Policlinico San Martino, Division of Clinical Neurophysiology and Epilepsy Center, Genoa, Italy
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Chen X, Feng L, Li J, Jiang H. Multiple system atrophy mimics CASPR2 antibody-associated disease: a case report. Neurodegener Dis Manag 2024; 14:69-74. [PMID: 39319563 PMCID: PMC11457613 DOI: 10.1080/17582024.2024.2388506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 07/15/2024] [Indexed: 09/26/2024] Open
Abstract
Aim: Multiple system atrophy (MSA) and CASPR2 antibody-associated disease bear their own characteristics.Case presentation: A 58-year-old woman presented with a 26 months history of uncoordinated gait and slurred speech. Her serum was positive for anti-CASPR2 antibodies, and MRI revealed atrophy of the brainstem and cerebellum. She underwent three plasma exchanges (PE) and received high doses of corticosteroids without any apparent effect. Her autonomic dysfunction improved after repetitive transcranial magnetic stimulation. Eventually, a diagnosis of MSA-cerebellar phenotype(MSA-C) was made.Conclusion: With increased availability of tools for neuron antibody detection, physicians need to be aware of the possibility that antibodies may accompany other diseases. This report underscores the modern dilemmas caused by available and extensive neuron antibody testing.
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Affiliation(s)
- Xiaoli Chen
- Department Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710008, China
| | - Li Feng
- Department Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Jing Li
- Department Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Hong Jiang
- Department Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
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Jurcau MC, Jurcau A, Diaconu RG, Hogea VO, Nunkoo VS. A Systematic Review of Sporadic Creutzfeldt-Jakob Disease: Pathogenesis, Diagnosis, and Therapeutic Attempts. Neurol Int 2024; 16:1039-1065. [PMID: 39311352 PMCID: PMC11417857 DOI: 10.3390/neurolint16050079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 09/09/2024] [Accepted: 09/14/2024] [Indexed: 09/26/2024] Open
Abstract
Creutzfeldt-Jakob disease is a rare neurodegenerative and invariably fatal disease with a fulminant course once the first clinical symptoms emerge. Its incidence appears to be rising, although the increasing figures may be related to the improved diagnostic tools. Due to the highly variable clinical picture at onset, many specialty physicians should be aware of this disease and refer the patient to a neurologist for complete evaluation. The diagnostic criteria have been changed based on the considerable progress made in research on the pathogenesis and on the identification of reliable biomarkers. Moreover, accumulated knowledge on pathogenesis led to the identification of a series of possible therapeutic targets, although, given the low incidence and very rapid course, the evaluation of safety and efficacy of these therapeutic strategies is challenging.
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Affiliation(s)
- Maria Carolina Jurcau
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (M.C.J.)
| | - Anamaria Jurcau
- Department of Psycho-Neurosciences and Rehabilitation, University of Oradea, 410087 Oradea, Romania
| | - Razvan Gabriel Diaconu
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (M.C.J.)
| | - Vlad Octavian Hogea
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (M.C.J.)
| | - Vharoon Sharma Nunkoo
- Neurorehabilitation Ward, Clinical Emergency County Hospital Bihor, 410169 Oradea, Romania
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Liao D, Zhu S, Yang L, Zhang C, He F, Yin F, Peng J. Clinical characteristics and long-term outcome of CASPR2 antibody-associated autoimmune encephalitis in children. Ital J Pediatr 2024; 50:158. [PMID: 39183357 PMCID: PMC11346287 DOI: 10.1186/s13052-024-01727-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/06/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Contactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum. METHODS Children who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected. RESULTS Patients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months). CONCLUSIONS CASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.
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Affiliation(s)
- Donglei Liao
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
| | - Saying Zhu
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
| | - Lifen Yang
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
| | - Ciliu Zhang
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
| | - Fang He
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
| | - Fei Yin
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China
- Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province, Central South University, XiangyaHospital, Changsha, 410008, China
| | - Jing Peng
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China.
- Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province, Central South University, XiangyaHospital, Changsha, 410008, China.
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Chen HY, Wang J, Song DY, Wang B, Xu ZY, Wu Q, Wang ZL. Anti-contact protein-associated protein 2 antibody encephalitis in children: A case report. World J Clin Cases 2024; 12:4365-4371. [PMID: 39015900 PMCID: PMC11235534 DOI: 10.12998/wjcc.v12.i20.4365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/07/2024] [Accepted: 05/20/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is an autoimmune disorder characterized by the presence of antibodies against the voltage-gated potassium channel. This leads to neurological symptoms, such as seizures, cognitive decline, and neuropathic pain, primarily affecting the limbic system. The prognosis of this disorder varies among individuals. CASE SUMMARY The patient, a girl aged nine years and nine months, underwent treatment for 14 to 21 d. The main clinical manifestations were vomiting and unclear consciousness, positive pathological signs, normal cranial computed tomography and magnetic resonance imaging, and abnormal electroencephalogram. The child was discharged after receiving immunoglobulin and hormone treatment. Subsequent follow-up over a period of 15 months after discharge, conducted through telephone and outpatient visits, showed no recurrence of symptoms. CONCLUSION Anti-CASPR2 antibody autoimmune encephalitis in children is rare, mainly manifested as convulsions, mental abnormalities, cognitive impairment, and neuropathic pain, among others. Timely evaluation for autoimmune encephalitis antibodies is crucial, especially in cases of recurrent central nervous system involvement in children.
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Affiliation(s)
- Hong-Yun Chen
- Department of Paediatrics, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
| | - Juan Wang
- Department of Paediatrics, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
| | - Dan-Yang Song
- Department of Paediatric Emergency Medicine, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Bin Wang
- Department of Paediatrics, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
| | - Zhi-Yun Xu
- Department of Paediatrics, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
| | - Qian Wu
- Department of Paediatrics, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
| | - Zhi-Liang Wang
- Department of Neurosurgery, Cangzhou Fourth Hospital (Nanpi County People’s Hospital), Cangzhou 061500, Hebei Province, China
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Lopes S, Francisco L, Moreira S, Varanda S, Araújo JM. Anti-CASPR2 Antibody-Associated Syndrome Presenting With Episodic Ataxia. Cureus 2024; 16:e59821. [PMID: 38846209 PMCID: PMC11156247 DOI: 10.7759/cureus.59821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2024] [Indexed: 06/09/2024] Open
Abstract
The anti-CASPR2 antibody-associated syndrome is a rare immune-mediated disorder. Most case reports describe neurologic symptoms that include encephalic signs, peripheral nerve hyperexcitability, dysautonomia, or neuropathic pain. We report the case of a 70-year-old man, admitted to the emergency department with complaints of slurred speech and imbalance. Neurological examination was relevant for dysarthria, hyperreflexia, and pancerebellar syndrome. Cranial CT and basic laboratory tests were normal and he spontaneously recovered after 14 hours. Over the next four months, the patient experienced three similar episodes in relation to stressful events (emotional and organic disturbances like prolonged fasting and vaccination). A contrast-enhanced MRI was performed, along with extensive laboratory testing, analysis of cerebrospinal fluid (CSF), paraneoplastic investigation, and next-generation sequencing panel for episodic ataxias. The results revealed oligoclonal bands in the CSF and positive anti-CASPR2 antibodies both in serum and CSF. Three-day-IV- methylprednisolone pulse followed by plasmapheresis and monthly intravenous immunoglobulins was performed with good response. In conclusion, the neurological manifestations that led to the diagnosis of anti-CASPR2 antibody-associated syndrome were intermittent self-limiting episodes of ataxia, often triggered by concurrent stress-inducing factors. This case supports the aim of other authors to add paroxysmal cerebellar ataxia to the spectrum of the anti-CASPR2 antibody syndrome.
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Affiliation(s)
- Sofia Lopes
- Neurology Department, Unidade Local de Saúde de Braga, Braga, PRT
| | - Leonor Francisco
- Neurology Department, Unidade Local de Saúde Alto Minho, Viana do Castelo, PRT
| | - Stefanie Moreira
- Neurology Department, Unidade Local de Saúde de Braga, Braga, PRT
| | - Sara Varanda
- Neurology Department, Unidade Local de Saúde de Braga, Braga, PRT
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Kelly MJ, Grant E, Murchison AG, Binks S, Ramanathan S, Michael S, Handel AE, Handunnetthi L, Uy CE, Soltys JN, Dubey D, Day GS, Lopez-Chiriboga AS, Flanagan EP, Sheerin F, Irani SR. Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis. JAMA Neurol 2024; 81:525-533. [PMID: 38497971 PMCID: PMC10949153 DOI: 10.1001/jamaneurol.2024.0126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/12/2024] [Indexed: 03/19/2024]
Abstract
Importance Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. Objective To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). Design, Setting, and Participants This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. Main Outcomes and Measures MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. Results Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala. Conclusions and Relevance In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.
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Affiliation(s)
- Mark J. Kelly
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Eleanor Grant
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
| | - Andrew G. Murchison
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Sophie Binks
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
| | - Sudarshini Ramanathan
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Translational Neuroimmunology Group, Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
- Department of Neurology, Concord Hospital, Sydney, Australia
| | - Sophia Michael
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- Department of Neurology, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Adam E. Handel
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
| | - Lahiru Handunnetthi
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
| | - Christopher E. Uy
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- Division of Neurology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - John N. Soltys
- Department of Neurosciences, Mayo Clinic, Jacksonville, Florida
| | | | - Gregory S. Day
- Department of Neurosciences, Mayo Clinic, Jacksonville, Florida
- Department of Neurology, Mayo Clinic, Jacksonville, Florida
| | | | | | - Fintan Sheerin
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Sarosh R. Irani
- Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- Department of Neurosciences, Mayo Clinic, Jacksonville, Florida
- Department of Neurology, Mayo Clinic, Jacksonville, Florida
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Sindhu DM, Rao S, Mahadevan A, Netravathi M. Clinicopathological Features in Morvan's Syndrome: An Autopsy Case Study. Neurol India 2024; 72:375-378. [PMID: 38817173 DOI: 10.4103/ni.ni_692_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 08/02/2023] [Indexed: 06/01/2024]
Abstract
Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.
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Affiliation(s)
| | - Shilpa Rao
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
| | - Anita Mahadevan
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
| | - M Netravathi
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
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Budhram A, Sechi E. Antibodies to neural cell surface and synaptic proteins in paraneoplastic neurologic syndromes. HANDBOOK OF CLINICAL NEUROLOGY 2024; 200:347-364. [PMID: 38494289 DOI: 10.1016/b978-0-12-823912-4.00006-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Among patients with paraneoplastic neurologic syndromes (PNS), emphasis has historically been placed on neural antibodies against intracellular proteins that have a strong association with malignancy. Because of the intracellular location of their antigenic targets, these antibodies are typically considered to be non-pathogenic surrogate markers of immune cell-mediated neural injury. Unfortunately, patients with these antibodies often have suboptimal response to immunotherapy and poor prognosis. Over the last two decades, however, dramatic advancements have been made in the discovery and clinical characterization of neural antibodies against extracellular targets. These antibodies are generally considered to be pathogenic, given their potential to directly alter antigen structure or function, and patients with these antibodies often respond favorably to prompt immunotherapy. These antibodies also associate with tumors and may thus occur as PNS, albeit more variably than neural antibodies against intracellular targets. The updated 2021 PNS diagnostic criteria, which classifies antibodies as high-risk, intermediate-risk, or lower-risk for an associated cancer, better clarifies how neural antibodies against extracellular targets relate to PNS. Using this recently created framework, the clinical presentations, ancillary test findings, oncologic associations, and treatment responses of syndromes associated with these antibodies are discussed.
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Affiliation(s)
- Adrian Budhram
- Department of Clinical Neurological Sciences, Western University, London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London Health Sciences Centre, London, ON, Canada.
| | - Elia Sechi
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
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Moura J, Carneiro P, Neves E, Santos E. Isolated Adie Pupil Associated With Anti-CASPR2 Antibodies. J Neuroophthalmol 2023; 43:e247-e248. [PMID: 35439231 DOI: 10.1097/wno.0000000000001598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- João Moura
- Department of Neurology (JM, ES), Centro Hospitalar Universitário do Porto, Porto, Portugal; Immunology Department (PC, EN), Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine (UMIB) (PC, EN, ES), Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Porto, Portugal; and Clinical Immunology Unit (ES), Centro Hospitalar Universitário do Porto, Porto, Portugal
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Moura J, Samões R, Cardoso M, Sousa AP, Damásio J, Marinho A, Carneiro P, Neves E, Silva AM, Santos E. Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes. Clin Neurol Neurosurg 2023; 234:107994. [PMID: 37797365 DOI: 10.1016/j.clineuro.2023.107994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/24/2023] [Accepted: 09/27/2023] [Indexed: 10/07/2023]
Abstract
INTRODUCTION Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.
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Affiliation(s)
- João Moura
- Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal.
| | - Raquel Samões
- Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine (UMIB), Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Porto, Portugal; Clinical Immunology Unit, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Márcio Cardoso
- Department of Neurophysiology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ana Paula Sousa
- Department of Neurophysiology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Joana Damásio
- Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - António Marinho
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Porto, Portugal; Clinical Immunology Unit, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Paula Carneiro
- Immunology laboratory, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Esmeralda Neves
- Immunology laboratory, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ana Martins Silva
- Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine (UMIB), Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Porto, Portugal; Clinical Immunology Unit, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ernestina Santos
- Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine (UMIB), Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Porto, Portugal; Clinical Immunology Unit, Centro Hospitalar Universitário do Porto, Porto, Portugal
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Cheng YK, Ling YZ, Yang CF, Li YM. Contactin-associated protein-like 2 antibody-associated autoimmune encephalitis in children: case reports and systematic review of literature. Acta Neurol Belg 2023; 123:1663-1678. [PMID: 36662402 PMCID: PMC9857898 DOI: 10.1007/s13760-023-02174-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/05/2023] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To ascertain the clinical characteristics of pediatric patients with contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis (AEs). METHODS Two cases of CASPR2 antibody-associated AEs have been reported. In addition, a systematic search of literature published between January 2010 and March 2022 through six online databases was conducted to identify the pediatric patients with CASPR2 antibody-associated AEs. Data on demographics, clinical symptoms, laboratory examinations, imaging, treatment, and outcome were collected. RESULTS Our updated literature search yielded 1,837 publications, of which 21 were selected, and 40 patients in this study met the diagnostic criteria for AE. There were 25 males and 15 females with a mean age of 9.2 years. The most common presenting symptoms are psychiatric symptoms (72.5%), sleep changes (62.5%), and movement disorders (60%). The psychiatric symptoms included mood changes (39.1%), behavior changes (25%), and hallucination (7.5%). In total, 23 cases (57.5%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, cardiovascular-related symptoms, and sweating. No tumors were observed in children. Thirty-eight patients received first-line immunotherapy, and eight received first-line and second-line immunotherapy. All patients had a good clinical response to immune therapy. Mean mRS at onset was 3.4; It was 0.88 at the last follow-up. There was no recurrence during follow-up. CONCLUSION Psychiatric symptoms, sleep disorders, movement disorders, and cardiovascular-related symptoms are the most common presentation in pediatric patients with CASPR2 antibody-associated AEs. Tumor, particularly with thymoma, is uncommon in children diagnosed with CASPR2 antibody-associated AEs. In addition, prompt diagnosis and immunotherapy can relieve symptoms and improve the prognosis.
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Affiliation(s)
- Yong-kang Cheng
- Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021 Jilin China
| | - Yao-zheng Ling
- Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021 Jilin China
| | - Chun-feng Yang
- Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021 Jilin China
| | - Yu-mei Li
- Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021 Jilin China
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Hu W, Wang E, Fang H, Li L, Yi J, Liu Q, Qing W, Guo D, Tan Q, Liao H. Clinical spectrum of contactin-associated protein 2 autoimmune encephalitis in children. Front Neurosci 2023; 17:1106214. [PMID: 37274200 PMCID: PMC10232858 DOI: 10.3389/fnins.2023.1106214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 04/03/2023] [Indexed: 06/06/2023] Open
Abstract
Objective Anti-contactin-associated protein 2 (CASPR2)-related autoimmune encephalitis (AE) is more common in adults than in children. Clinical understanding of anti-CASPR2-antibody (Ab)-related AE, diagnosis and treatment standards are lacking in children. Therefore, this retrospective study on clinical symptoms and treatment outcomes in children with anti-CASPR2-Ab-related AE was conducted, to improve the clinical understanding of the disease, its diagnosis and treatment. Methods This study retrospectively assessed children with anti-CASPR2-Ab-related AE from January 1, 2020, to June 30, 2022, in the Department of Neurology at Hunan Children's Hospital. Data regarding demographics, clinical symptoms, laboratory examinations, electroencephalography (EEG), imaging, and curative were collected. Results Thirteen patients were positive for serum anti-CASPR2-Ab (age at manifestation, 25 months to 13 years old; median, 8.1 years old; male-to-female ratio, 8/5). One patient (P1) had dual Abs, including anti-CASPR2 and anti-N-methyl-D-aspartate receptor Abs; his symptoms were more severe than those of children with anti-CASPR2 Abs alone. The clinical symptoms of the 13 patients with anti-CASPR2 Ab were movement disorders (9/13), consciousness disorders (9/13), abnormal demeanor (8/13), seizures (7/13), language disorders (6/13), fever (6/13), pain (4/13), involuntary exercise (4/13), poor diet (4/13), vomiting (3/13), sleep disorders (3/13), mood disorders (3/13), eczema/itching/redness (2/13), sweating (P8), urinary disorders (P13), and cognitive disorders (P9). No tumors were found in any patient. Additionally, EEG results of six patients were abnormal and imaging findings such as abnormal signals were found in 10 patients. Moreover, all except one patient recovered well after treatment; P1 with overlapping syndrome underwent recovery for more than 2 years. None of the patients who recovered have had a relapse. Discussion and conclusion Anti-CASPR2-Ab-related AE has several clinical manifestations. Anti-CASPR2-Ab levels were higher in male patients than in female patients. Moreover, related tumors are relatively rare. Most patients benefit from immunotherapy and have a lower chance of recurrence in the short term. Furthermore, different from patients who had anti-CASPR2-Ab AE alone, those with overlapping syndrome had a severe and complex condition requiring lengthy treatment and rehabilitation. Additional studies are needed to evaluate the long-term prognosis of these patients.
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Affiliation(s)
- Wenjing Hu
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Enhui Wang
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Hongjun Fang
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Li Li
- Department of Radiology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Jurong Yi
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Qingqing Liu
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Wei Qing
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Danni Guo
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Qianqian Tan
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
| | - Hongmei Liao
- Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan, China
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Marsili L, Marcucci S, LaPorta J, Chirra M, Espay AJ, Colosimo C. Paraneoplastic Neurological Syndromes of the Central Nervous System: Pathophysiology, Diagnosis, and Treatment. Biomedicines 2023; 11:biomedicines11051406. [PMID: 37239077 DOI: 10.3390/biomedicines11051406] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/04/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. PNS associated with antibodies against intracellular antigens, known as "high-risk" antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as "intermediate- or low-risk" antibodies, are less frequently associated with cancer. In this narrative review, we will focus on PNS of the central nervous system (CNS). Clinicians should have a high index of suspicion with acute/subacute encephalopathies to achieve a prompt diagnosis and treatment. PNS of the CNS exhibit a range of overlapping "high-risk" clinical syndromes, including but not limited to latent and overt rapidly progressive cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome, paraneoplastic (and limbic) encephalitis/encephalomyelitis, and stiff-person spectrum disorders. Some of these phenotypes may also arise from recent anti-cancer treatments, namely immune-checkpoint inhibitors and CAR T-cell therapies, as a consequence of boosting of the immune system against cancer cells. Here, we highlight the clinical features of PNS of the CNS, their associated tumors and antibodies, and the diagnostic and therapeutic strategies. The potential and the advance of this review consists on a broad description on how the field of PNS of the CNS is constantly expanding with newly discovered antibodies and syndromes. Standardized diagnostic criteria and disease biomarkers are fundamental to quickly recognize PNS to allow prompt treatment initiation, thus improving the long-term outcome of these conditions.
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Affiliation(s)
- Luca Marsili
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH 45219, USA
| | - Samuel Marcucci
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH 45219, USA
| | - Joseph LaPorta
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH 45219, USA
| | - Martina Chirra
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45219, USA
| | - Alberto J Espay
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH 45219, USA
| | - Carlo Colosimo
- Department of Neurology, Santa Maria University Hospital, 05100 Terni, Italy
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Goovaerts S, Gens R, Seynaeve L, Engelborghs S, Vandervorst F. Anti-CASPR2 antibody-associated limbic encephalitis in a patient with a squamous cell carcinoma of the throat. Acta Neurol Belg 2023:10.1007/s13760-023-02272-4. [PMID: 37119470 PMCID: PMC10148571 DOI: 10.1007/s13760-023-02272-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 04/06/2023] [Indexed: 05/01/2023]
Affiliation(s)
- Sarah Goovaerts
- Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
- Center 4 Neurosciences (C4N), Neuroprotection and Neuromodulation (NEUR) Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
| | - Robin Gens
- Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center 4 Neurosciences (C4N), Neuroprotection and Neuromodulation (NEUR) Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Laura Seynaeve
- Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center 4 Neurosciences (C4N), Neuroprotection and Neuromodulation (NEUR) Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Sebastiaan Engelborghs
- Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center 4 Neurosciences (C4N), Neuroprotection and Neuromodulation (NEUR) Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Fenne Vandervorst
- Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center 4 Neurosciences (C4N), Neuroprotection and Neuromodulation (NEUR) Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
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Ferrara JM, Wiid M, Burke S. Contactin-Associated Protein-Like 2-Related Peripheral Nerve Hyperexcitability Associated With Charcot-Marie-Tooth Type 4F. Neurohospitalist 2023; 13:164-168. [PMID: 37064943 PMCID: PMC10091429 DOI: 10.1177/19418744221140182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
Contactin-associated protein-like 2 autoimmunity is an uncommon disorder resulting in peripheral nerve hyperexcitability or encephalitis. In a fifth of cases, onset may be provoked by thymoma, but other associations are largely unknown. We report a patient with anti-contactin-associated protein-like 2-related peripheral nerve hyperexcitability arising in the setting of Charcot-Marie-Tooth type 4F and discuss potential mechanisms underlying the association.
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Affiliation(s)
- Joseph M. Ferrara
- Division of Neurology, Department of
Internal Medicine, East Carolina University School of
Medicine, Greenville, NC, USA
- Department of Internal Medicine, Virginia Tech Carilion, Roanoke, VA, USA
| | - Michael Wiid
- Department of Internal Medicine, Virginia Tech Carilion, Roanoke, VA, USA
| | - Sean Burke
- Department of Internal Medicine, Virginia Tech Carilion, Roanoke, VA, USA
- Comprehensive Neurology Services, Frederick Health, Frederick, MD, USA
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Song W, Li K, Li J, Liu X, Wu X, Xu X, Xiong K, Chen X, Zhang Y. Thymoma-associated autoimmune encephalitis: Analysis of factors determining prognosis. CNS Neurosci Ther 2023; 29:1213-1221. [PMID: 36914970 PMCID: PMC10068466 DOI: 10.1111/cns.14166] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 03/16/2023] Open
Abstract
INTRODUCTION Autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders caused by a misdirected immune response against self-antigens expressed in the central nervous system. The thymus is a central organ in the immune system and thymic tumors are thought to be possible initiators of many neurological disorders. Recently, there is growing evidence that thymomas are associated with autoimmune encephalitis. AIMS Our study initially explored the characteristics of patients with autoimmune encephalitis combined with thymoma. METHODS We used patient data from January 1, 2011 to October 1, 2021 from the PubMed, Web of Science, Ovid, and CNKI platforms to analyze overall demographics, frequency of symptoms and associations, and treatment prognosis outcomes. RESULTS A total of 68 patients were included. There were 39 female cases (57.4%). The mean age was 50 years (IQR 40-66 years). All had acute and subacute onset. The clinical manifestations were mostly cognitive changes (70.6%), mental disorders (57.4%), and epilepsy (50.0%). The most common neuronal antibody was alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Magnetic resonance imaging (MRI) abnormalities were present in 81.0% of patients, mostly in the hippocampus, temporal lobe, and some in cortical and subcortical areas. Abnormalities in the electroencephalogram (EEG) in 69.8% of patients. Treatment involved immunotherapy and thymoma treatment, with 79.7% of patients improving after treatment. While 20.3% of patients had a poor prognosis. Further, 14.8% of patients relapsed. Mental disorders, autonomic dysfunction, sleep disturbances, anti-Ma2, and thymoma untreated were more frequent in patients with poor prognosis. CONCLUSION Thymoma-associated autoimmune encephalitis is a unique disease entity. Long-term follow-up of chest CT findings is recommended for patients with autoimmune encephalitis.
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Affiliation(s)
- Wenli Song
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Keru Li
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiao Li
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaoni Liu
- Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Fudan University, Shanghai, China
| | - Xiaoke Wu
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaodong Xu
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Kangping Xiong
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiangjun Chen
- Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Fudan University, Shanghai, China.,Human Phenome Institute, Fudan University, Shanghai, China
| | - Yanlin Zhang
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
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Paraneoplastic neurological syndromes of the central nervous system: a single institution 7-year case series. Acta Neurol Belg 2023:10.1007/s13760-023-02232-y. [PMID: 36884202 PMCID: PMC9994403 DOI: 10.1007/s13760-023-02232-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 03/02/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND Paraneoplastic neurological syndromes (PNSs) are nonmetastatic complications of malignancy, defined by the presence of onconeural antibodies (ONAs). ONAs may be found in 60% of patients with central nervous system (CNS) involvement, and they are directed against intraneuronal antigens or channels, receptors or associated proteins located at the synaptic or extra-synaptic neuronal cell membrane. Given its rare incidence, there are few epidemiological case series on CNS-PNS. We aim to discuss the variability of CNS-PNSs etiology, clinical features, management and outcome, highlighting the importance of early recognition and appropriate treatment, leading to significant reduction of mortality and morbidity. METHODS We retrospectively reviewed our 7-years single-center experience, and specifically discussed the underlying etiology, parenchymal CNS involvement, and the acute treatment response. Only cases fulfilling PNS Euronetwork criteria for definitive PNS were included. RESULTS A total of 26 probable PNSs cases involving CNS were identified. We reported medical records of eleven (42.3%) illustrative cases, meeting the criteria of definite PNS and presenting variable clinical spectrum and different radiological appearances. Our series has a relative paucity of the most common syndromes and larger portion of clinical diagnosis with ONAs. Well-characterized ONAs had been detected in CSF of six patients. CONCLUSIONS Our case series supports the utmost importance of early recognition of CNS-PNSs. Screening for occult malignancies should not be limited to patients with classical CNS syndrome. Empiric immunomodulatory therapy may be considered before the diagnostic evaluation is completed, in order to prevent unfavorable outcome. Late presentations should not discourage initiation of treatment.
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Wu L, Cai F, Zhuo Z, Wu D, Zhang T, Yang H, Fang H, Xiao Z. CASPR2 antibody associated neurological syndromes in children. Sci Rep 2023; 13:2073. [PMID: 36747031 PMCID: PMC9902610 DOI: 10.1038/s41598-023-28268-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 01/16/2023] [Indexed: 02/08/2023] Open
Abstract
To strengthen the understanding of the clinical features for CASPR2 neurological autoimmunity in children. A multicenter retrospective and prospective analysis of CASPR2 autoimmunity was conducted. Twenty-six patients were enrolled, including 25 with serum positivity and 3 with cerebrospinal fluid (CSF) positivity; 5 patients were co-positive with anti-NMDAR or anti-GABABR antibodies. Eleven patients (who manifested with refractory epilepsy, psychobehavioral abnormalities or germinoma) presented with low antibody titers, relatively normal MRI/EEG/CSF examinations, and poor response to immunotherapy and were thus considered false positive (42.3%). Fifteen patients were diagnosed with autoimmune encephalitis/ encephalopathy/ cerebellitis (including 1 whose condition was secondary to Japanese encephalitis). The most common symptoms included disorders of consciousness (10/15), fever (8/15), psychological symptoms/abnormal behaviors (8/15), sleep disorders (8/15), seizures (7/15), movement disorders (5/15), autonomic symptoms (5/15). Brain MRI revealed abnormalities in 10 patients (66.7%). Electroencephalography (EEG) recordings revealed a slow wave background in 13 patients (86.7%). Five patients showed elevated WBCs in CSF, and 4 patients showed elevated protein levels in the CSF. Thirteen patients received immunotherapy (rituximab was adopted in 2 cases) and recovered well. Two patients received symptomatic treatment, and the recovery was slow and accompanied by emotional abnormalities and developmental delay. Autoimmune encephalitis is the most common clinical phenotype; it can be secondary to Japanese encephalitis. Rituximab can be used in patients who respond poorly to conventional immunotherapy. The high false-positive rate of anti-CASPR2 in refractory epilepsy and the psychobehavioral abnormalities needs to be explored further.
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Affiliation(s)
- Liwen Wu
- Neurology department, Hunan Children's Hospital, The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, Hunan, China
| | - Fang Cai
- Neurology department, Chenzhou Children's Hospital, Chengzhou, Hunan, China
| | - Zhihong Zhuo
- Pediatric Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Dejun Wu
- Longshan People's Hospital, Xiangxi Autonomous Prefecture, Hunan, China
| | | | - Haiyang Yang
- Neurology department, Hunan Children's Hospital, The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, Hunan, China
| | - Hongjun Fang
- Neurology department, Hunan Children's Hospital, The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, Hunan, China
| | - Zhenghui Xiao
- Hunan Key Laboratory of Pediatric Emergency Medicine, Hunan Children's Hospital, The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, Hunan, China.
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Chen Z, Tang J. Case report: Autoimmune encephalitis associated with anti-CASPR2 antibody mimicking cerebral infarction. Front Immunol 2023; 14:1041664. [PMID: 36776888 PMCID: PMC9909330 DOI: 10.3389/fimmu.2023.1041664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 01/13/2023] [Indexed: 01/28/2023] Open
Abstract
Autoimmune encephalitis associated with antibody against contactin-associated protein-like 2 (CASPR2) varies in its clinical presentation. The disease is difficult to distinguish from some other conditions without testing for anti-CASPR2 antibody in blood serum or cerebrospinal fluid. Cerebral lesions are typically detected by magnetic resonance imaging (MRI) in the medial temporal lobe or hippocampus. Here, we describe a patient with anti-CASPR2 antibody autoimmune encephalitis whose imaging manifestations mimicked infarction in the left frontal lobe. The 48-year-old man reported memory loss, convulsions, and disturbed consciousness one day after drinking wine. The right upper arm showed reduced autonomous movement after painful stimuli, and MRI showed abnormal hyperintensities in the left frontal lobe on T2 and fluid-attenuated inversion recovery sequences, restricted diffusion, and decreased cerebral blood flow, mimicking acute cerebral infarction. Contrast-enhanced T1-weighted MRI showed gyral enhancement involving the cortex and subcortical white matter. Computed tomography angiography did not identify culprit blood vessels. Symptoms did not improve with anti-platelet or lipid-lowering therapy. Screening for serum antibodies associated with autoimmune encephalitis detected antibody against CASPR2, and intravenous immunoglobulin therapy substantially improved symptoms. This case provides the first indication that anti-CASPR2 antibody-associated autoimmune encephalitis can manifest as involvement of the cortex and subcortical white matter in the frontal lobe based on MRI. It emphasizes the need for thorough investigation, including analysis of potential autoimmunity, of patients whose imaging findings mimic ischemic infarction.
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Yuan W, Xiaofei G, Xiangming Y, Jinbo C, Yuliang W. MELAS syndrome with anti-Caspr2 autoantibody positivity: a case report. Acta Neurol Belg 2022:10.1007/s13760-022-02135-4. [DOI: 10.1007/s13760-022-02135-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022]
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Benoit J, Muñiz-Castrillo S, Vogrig A, Farina A, Pinto AL, Picard G, Rogemond V, Guery D, Alentorn A, Psimaras D, Rheims S, Honnorat J, Joubert B. Early-Stage Contactin-Associated Protein-like 2 Limbic Encephalitis: Clues for Diagnosis. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2022; 10:10/1/e200041. [PMID: 36288995 PMCID: PMC9608385 DOI: 10.1212/nxi.0000000000200041] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 08/19/2022] [Indexed: 11/05/2022]
Abstract
Background and Objectives Previous studies suggested that autoimmune limbic encephalitis with antibodies against contactin-associated protein-like 2 (CASPR2-encephalitis) is clinically heterogeneous and progresses slowly, preventing its early recognition. We aimed to describe the onset and progression of CASPR2-encephalitis and to assess long-term outcomes. Methods We retrospectively analyzed the medical records of all patients whose CSF tested positive for anti-CASPR2 antibodies in our center between 2006 and 2020. Standardized telephone interviews of all available patients and relatives were conducted, assessing long-term functional independence using the Functional Activity Questionnaire (FAQ) and quality of life using the 36-Item Short-Form Survey (SF36). Results Forty-eight patients were included (98% males; median age 64 years), and 35 participated in telephone interviews (73%). At onset, 81% had at least 1 neurologic symptom among the following: limbic (54%), peripheral nerve hyperexcitability (PNH; 21%), and/or cerebellar symptoms (17%). Most of the patients (75%) had initially symptoms of only one of these categories. Limbic symptoms at onset included mostly seizures (33%), while memory disturbances were less frequent (10%). PNH signs were mostly neuropathic pain (9/10 patients). Other symptoms seen at onset included asthenia (33%), mood disorders (25%), and insomnia (21%); 19% of patients did not show any limbic, peripheral, or cerebellar symptom at onset but only asthenia (15%), mood disorders (6%), weight loss (8%), dysautonomia (4%), and/or insomnia (2%). The peak of the disease was attained in median 16.7 months after onset. Over the study period (median follow-up, 58.8 months, range 10.6–189.1), 77% of patients developed ≥3 core CASPR2 symptoms and 42% fulfilled the diagnostic criteria for autoimmune limbic encephalitis, although all patients ultimately developed limbic symptoms. At the last visit, most interviewed patients (28/35 patients, 80%; median, 5 years after onset) had recovered functional independence (FAQ <9) while only the vitality subscore of the SF36 was lower than normative data (mean 49.9 vs 58.0, p = 0.0369). Discussion CASPR2-encephalitis has a progressive course and is highly heterogeneous at the early stage. In men older than 50 years, otherwise unexplained seizures, cerebellar ataxia, and/or neuropathic pain are suggestive of early-stage CASPR2-encephalitis, especially if they coincide with recent asthenia, mood disorders, or insomnia.
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Affiliation(s)
- Jeanne Benoit
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Sergio Muñiz-Castrillo
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Alberto Vogrig
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Antonio Farina
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Anne-Laurie Pinto
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Geraldine Picard
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Veronique Rogemond
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Deborah Guery
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Agusti Alentorn
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Dimitri Psimaras
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Sylvain Rheims
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Jérôme Honnorat
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France
| | - Bastien Joubert
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Hospices Civils de Lyon; Synaptopathies and Autoantibodies (SynatAc) Team (J.B., S.M.-C., A.V., A.F., A.-L.P., G.P., V.R., J.H., B.J.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Epileptology-EEG Department (J.B.), Neurology, Pasteur2 Hospital, University Hospitals of Nice; Côte d'Azur University (J.B.), UR2CA, URRIS, Pasteur2 Hospital, University Hospitals of Nice; Department of Functional Neurology and Epileptology (D.G., S.R.), Hospices Civils de Lyon, France; European Network for Rare and Complex Epilepsies (EPICARE) (D.G., S.R.); Service de Neurologie 2-Mazarin (A.A., D.P.), Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, APHP; Inserm U1127 CNRS UMR 7225 (A.A., D.P.), Institut Du Cerveau et de la Moelle épinière, ICM, Université Pierre-et-Marie-Curie, Sorbonne Universités, Paris; and Lyon's Neuroscience Research Center (S.R.), INSERM U1028/CNRS UMR 5292; Université Lyon 1 Claude Bernard, France.
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Li G, Liu X, Yu T, Ren J, Wang Q. Positron emission tomography in autoimmune encephalitis: Clinical implications and future directions. Acta Neurol Scand 2022; 146:708-715. [PMID: 36259555 DOI: 10.1111/ane.13717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 10/04/2022] [Accepted: 10/08/2022] [Indexed: 11/28/2022]
Abstract
18 F-fluoro-deoxyglucose position emission tomography (18 F-FDG-PET) has been proven as a sensitive and reliable tool for diagnosis of autoimmune encephalitis (AE). More attention was paid to this kind of imaging because of the shortage of MRI, EEG, and CSF findings. FDG-PET has been assessed in a few small studies and case reports showing apparent abnormalities in cases where MRI does not. Here, we summarized the patterns (specific or not) in AE with different antibodies detected and the clinical outlook for the wide application of FDG-PET considering some limitations. Specific patterns based on antibody subtypes and clinical symptoms were critical for identifying suspicious AE, the most common of which was the anteroposterior gradient in anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis and the medial temporal lobe hypermetabolism in limbic encephalitis. And the dynamic changes of metabolic presentations in different phases provided us the potential to inspect the evolution of AE and predict the functional outcomes. Except for the visual assessment, quantitative analysis was recently reported in some voxel-based studies of regions of interest, which suggested some clues of the future evaluation of metabolic abnormalities. Large prospective studies need to be conducted controlling the time from symptom onset to examination with the same standard of FDG-PET scanning.
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Affiliation(s)
- Gongfei Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xiao Liu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Tingting Yu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Jiechuan Ren
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Qun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Beijing Institute for Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
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29
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Muacevic A, Adler JR. Rituximab Was Effective in Relieving Symptoms of Isaacs Syndrome: A Case Report. Cureus 2022; 14:e30100. [PMID: 36381695 PMCID: PMC9642979 DOI: 10.7759/cureus.30100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2022] [Indexed: 11/22/2022] Open
Abstract
We presented a 23-year-old patient who had experienced neuromyotonia in his left leg. Although he tested negative for anti-LGI1 and anti-CASPR2 antibodies, we diagnosed him with Isaacs syndrome due to myokymic discharges on electromyography and symptoms being relieved by intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIg). IVMP, IVIg, plasma exchange, or cyclosporine treatment did not provide a long-term response; however, rituximab showed long-term improvement. Rituximab should be considered early in the treatment of patients with antibody-negative Isaacs syndrome who are responsive to immunotherapy, including IVMP, IVIg, and plasma exchange, and have long-term symptoms that are hard to control.
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30
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Ford H, Griffith S, Warren N, Swayne A, Blum S, Butzkueven H, O'Brien TJ, Velakoulis D, Kulkarni J, Monif M. Psychiatric manifestations of autoimmune encephalitis. Autoimmun Rev 2022; 21:103145. [PMID: 35840036 DOI: 10.1016/j.autrev.2022.103145] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/11/2022] [Indexed: 12/21/2022]
Abstract
Autoimmune encephalitis is increasingly recognized as a cause of psychiatric symptoms. A wide spectrum of psychiatric manifestations have been described which may precede, follow or occur independently of neurologic features. Patients typically respond to immunotherapy, however diagnosis is challenging due to phenotypic heterogeneity. The aim of this review is to provide an overview of the psychiatric features associated with encephalitis mediated by autoantibodies targeting neuronal cell-surface antigens and describe indicators of potential immunopathology underlying psychiatric manifestations.
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Affiliation(s)
- Hannah Ford
- Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
| | - Sarah Griffith
- Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia; Department of Neuroscience, Monash University, Melbourne, Vic, Australia
| | - Nicola Warren
- School of Medicine, University of Queensland, Brisbane, Australia; Metro South Addiction and Mental Health Service, Brisbane, Australia
| | - Adrew Swayne
- School of Medicine, University of Queensland, Brisbane, Australia; Princess Alexandra Hospital, Department of Neurology, Brisbane, Queensland, Australia
| | - Stefan Blum
- School of Medicine, University of Queensland, Brisbane, Australia; Princess Alexandra Hospital, Department of Neurology, Brisbane, Queensland, Australia
| | - Helmut Butzkueven
- Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia; Department of Neuroscience, Monash University, Melbourne, Vic, Australia
| | - Terence J O'Brien
- Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia; Department of Neuroscience, Monash University, Melbourne, Vic, Australia
| | - Dennis Velakoulis
- Neuropsychiatry, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Psychiatry, The University of Melbourne, Melbourne, Vic, Australia
| | - Jayashri Kulkarni
- Department of Psychiatry, Alfred Hospital, Melbourne, Vic, Australia; Department of Psychiatry, Monash University, Melbourne, Vic, Australia
| | - Mastura Monif
- Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Neuroscience, Monash University, Melbourne, Vic, Australia.
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31
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Guillain-Barré-like syndrome: an uncommon feature of CASPR2 and LGI1 autoimmunity. J Neurol 2022; 269:5893-5900. [PMID: 35781606 DOI: 10.1007/s00415-022-11248-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/08/2022] [Accepted: 06/20/2022] [Indexed: 10/17/2022]
Abstract
Contactin-associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) are essential components of the voltage-gated Kv1 potassium channel complex and are extensively expressed in both central and peripheral nervous system. Autoimmune CASPR2 and LGI1 disorders commonly present with Morvan syndrome (Mos) and/or limbic encephalitis, but whether Guillain-Barré syndrome (GBS) is a specific clinical phenotype is unknown. Here, we first reported an adult patient with dual CASPR2 and LGI1 antibodies in both serum and cerebrospinal fluid, who initially presented with a GBS-like syndrome and developed a typical MoS and respiratory paralysis, with a rapid resolution of his neurological symptoms and disappearance of autoantibodies after treatment with plasma exchange. Additionally, we also provided an overview of the previously reported GBS cases associated with CASPR2 or LGI1 antibodies. These cases expand the phenotypic spectrum of CASPR2 and LGI1 autoimmune syndromes, implying that these two antigens, especially CASPR2, are likely to participate in the etiology of GBS as a potential new target antigen, which deserves further exploration.
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32
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Nawfal O, Agha M, Makki A, Beydoun A. Refractory Morvan Syndrome Responsive to Rituximab: A Case Report and Review of the Literature. Neuromuscul Disord 2022; 32:682-686. [DOI: 10.1016/j.nmd.2022.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 05/30/2022] [Accepted: 06/01/2022] [Indexed: 11/30/2022]
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Jia Y, Li M, Li D, Zhang M, Wang H, Jiao L, Huang Z, Ye J, Liu A, Wang Y. Immune-Mediated Cerebellar Ataxia Associated With Neuronal Surface Antibodies. Front Immunol 2022; 13:813926. [PMID: 35250990 PMCID: PMC8891139 DOI: 10.3389/fimmu.2022.813926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 02/01/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Immune-mediated cerebellar ataxias (IMCAs) are common in paraneoplastic cerebellar degeneration (PCD) but rarely occur in patients with neuronal surface antibodies (NSAbs). Although cerebellar ataxias (CAs) associated with anti-NMDAR and anti-CASPR2 have been reported in a few cases, they have never been studied systematically. This study aimed to analyze the characteristics of anti-NSAbs-associated CAs. METHODS A retrospective investigation was conducted to identify patients using the keywords IMCAs and NSAbs. We collected the clinical data of 14 patients diagnosed with anti-NSAbs-associated CAs. RESULTS The median age was 33 years (16-66), and the male-to-female ratio was 4:3. Nine were positive for NMDAR-Ab, two for LGI1-Ab, two for CASPR2-Ab, and one for AMPA2R-Ab. CAs were initial symptoms in three patients and presented during the first two months of the disease course (10 days on average) among the rest of the patients. After the immunotherapy, two cases were free from symptoms, and eight cases recovered satisfactorily (10/14, 71.4%). Compared with other causes of IMCAs, anti-NSAbs were more frequently associated with additional extra-cerebellar symptoms (85.7%), mostly seizures (78.6%) and mental abnormalities (64.3%). In the CSF analysis, pleocytosis was detected in ten patients (71.4%) and oligoclonal bands (OB) were observed in nine patients (64.3%). Moreover, compared with PCD and anti-GAD65-Ab-associated CAs, anti-NSAbs-associated CAs showed a better response to immunotherapy. CONCLUSION IMCAs are rare and atypical in autoimmune encephalitis with neuronal surface antibodies. Compared with other forms of IMCAs, more symptoms of encephalopathy, a higher rate of pleocytosis and positive OB in CSF, and positive therapeutic effect were the key features of anti-NSAbs-associated CAs.
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Affiliation(s)
- Yu Jia
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Mingyu Li
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Dawei Li
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Mengyao Zhang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Huifang Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Lidong Jiao
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhaoyang Huang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Capital Medical University, Beijing, China.,Center of Epilepsy, Beijing Institute for Brain Disorders, Capital Medical University, Ministry of Science and Technology, Beijing, China.,Institute of Sleep and Consciousness Disorders, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
| | - Jing Ye
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Capital Medical University, Beijing, China.,Center of Epilepsy, Beijing Institute for Brain Disorders, Capital Medical University, Ministry of Science and Technology, Beijing, China
| | - Aihua Liu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Capital Medical University, Beijing, China.,Center of Epilepsy, Beijing Institute for Brain Disorders, Capital Medical University, Ministry of Science and Technology, Beijing, China
| | - Yuping Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Capital Medical University, Beijing, China.,Center of Epilepsy, Beijing Institute for Brain Disorders, Capital Medical University, Ministry of Science and Technology, Beijing, China.,Institute of Sleep and Consciousness Disorders, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
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Hsieh PC, Wu YR. Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders. J Mov Disord 2022; 15:95-105. [PMID: 35670020 PMCID: PMC9171305 DOI: 10.14802/jmd.21077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 04/16/2022] [Accepted: 04/18/2022] [Indexed: 11/24/2022] Open
Abstract
Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.
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Affiliation(s)
- Pei-Chen Hsieh
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Yih-Ru Wu
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- Department of Neurology, Chang Gung University, College of Medicine, Taoyuan, Taiwan
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35
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Seery N, Butzkueven H, O'Brien TJ, Monif M. Contemporary advances in antibody-mediated encephalitis: anti-LGI1 and anti-Caspr2 antibody (Ab)-mediated encephalitides. Autoimmun Rev 2022; 21:103074. [PMID: 35247644 DOI: 10.1016/j.autrev.2022.103074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 02/27/2022] [Indexed: 01/17/2023]
Abstract
Encephalitides with antibodies directed against leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2) represent two increasingly well characterised forms of autoimmune encephalitis. Both share overlapping and distinct clinical features, are mediated by autoantibodies directed against differing proteins complexed with voltage-gated potassium channels, with unique genetic predisposition identified to date. Herein we summarise disease mechanisms, clinical features, treatment considerations, prognostic factors and clinical outcomes regarding these disorders.
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Affiliation(s)
- Nabil Seery
- Department of Neuroscience, Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
| | - Helmut Butzkueven
- Department of Neuroscience, Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
| | - Terence J O'Brien
- Department of Neuroscience, Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
| | - Mastura Monif
- Department of Neuroscience, Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
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36
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Movement disorders associated with neuronal antibodies: a data-driven approach. J Neurol 2022; 269:3511-3521. [PMID: 35024921 PMCID: PMC8756747 DOI: 10.1007/s00415-021-10934-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/06/2021] [Indexed: 11/17/2022]
Abstract
Background Movement disorders can be associated with anti-neuronal antibodies. Methods We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert’s clinical feedback.
Results Three hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu.
Conclusion Selected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts.
Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10934-7.
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Joseph J, Brenton JN. Child with Suspected Autoimmune Encephalitis. SYMPTOM-BASED APPROACH TO PEDIATRIC NEUROLOGY 2022:625-638. [DOI: 10.1007/978-3-031-10494-7_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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38
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Jiang Y, Tan C, Li T, Song X, Ma J, Yao Z, Hong S, Li X, Jiang L, Luo Y. Phenotypic Spectrum of CASPR2 and LGI1 Antibodies Associated Neurological Disorders in Children. Front Pediatr 2022; 10:815976. [PMID: 35463890 PMCID: PMC9021408 DOI: 10.3389/fped.2022.815976] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 03/11/2022] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The clinical data of patients with double-positive for leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies is limited, particularly for children. This study aimed to investigate and summarize the clinical features and long-term prognosis of children's LGI1 and CASPR2 antibodies related to neurological disorders. METHODS We collected the clinical data and prognosis of patients with dual positive antibodies of CASPR2 and LGI1, hospitalized in the Department of Neurology, Children's Hospital of Chongqing Medical University. Furthermore, we summarized the clinical phenotypes of this disorder in children by reviewing the published literature. RESULTS Two patients presenting with variable neurological symptoms including pain, hypertension, profuse sweating, irritability, and dyssomnia from Children's Hospital of Chongqing Medical University were enrolled in this study. Together with the two patients, we identified 17 children with dual CASPR2 and LGI1 antibodies, including 12 males and 5 females. At the onset, the median age was 4.1 years (range 1-16, interquartile range 2.5-13.5), with 9 children younger than 5 years and 6 adolescents. Of the 17 patients, 11 were diagnosed with Morvan syndrome, 4 with acquired neuromyotonia, 1 with Guillain-Barré syndrome, and 1 with Guillain-Barré syndrome combined with Morvan syndrome. Dysautonomia (14/17, 82.3%), pain (13/17, 76.4%), sleep disorders (13/17, 76.4%), encephalopathy (12/17, 70.5%), and weight loss (10/17, 58.8%) were the most frequently described symptoms overall. No tumors were identified. Of the 17 patients, 13 received immunotherapy comprising IVIG combination of IVMP during the acute symptomatic phase followed by oral prednisolone to maintain remission (n = 7), the combination of IVIG, IVMP, oral prednisolone and methotrexate (n = 1), the combination of IVIG, IVMP, and mycophenolate mofetil (n = 1), the combination of IVIG, IVMP, oral prednisolone, and rituximab (n = 1), IVIG only (n = 2), IVMP only (n = 1). Median modified Rankin Scale (mRS) scores in the acute phase were 3 (range 1-4) and improved gradually. Over the follow-up (median 8.6 months, range 1-36 months), 52.9% (9/17) of the patients recovered completely; one patient relapsed and showed immunotherapy-dependent. CONCLUSION LGI1 and CASPR2 double-positive antibodies associated with the neurological diseases can occur in children of all ages and involve multiple nervous systems. Morvan syndrome is the most common phenotype of this disorder. The long-term outcomes are mostly favorable upon immunotherapy.
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Affiliation(s)
- Yan Jiang
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Chengbing Tan
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Tingsong Li
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Xiaojie Song
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Jiannan Ma
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Zhengxiong Yao
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Siqi Hong
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Xiujuan Li
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Li Jiang
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
| | - Yuanyuan Luo
- Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
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Dou Q, Li R, Shu X. Anti-contactin-associated protein-like 2 antibody-associated encephalitis in children: A case report and literature review. Front Pediatr 2022; 10:1004210. [PMID: 36340710 PMCID: PMC9630637 DOI: 10.3389/fped.2022.1004210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Anti-Contactin-associated protein-like 2 (CASPR2) antibody-associated encephalitis is a rare group of autoimmune diseases that causes extensive damage to the central and/or peripheral nervous system. CASE PRESENTATION Here, we reported a case of anti-CASPR2 antibody-associated encephalitis in a 12-year-old male patient with symptoms of headache, consciousness disturbance, mental abnormalities, urinary incontinence, fasciculations in the extremity muscles, and involuntary movements. The testing for autoimmune encephalitis-associated antibodies showed that CASPR2-associated antibodies were positive, and electroencephalography showed diffuse slow waves. No tumor was found after screening for malignancies. The child's status significantly improved after receiving immunotherapy with intravenous methylprednisolone and immunoglobulin. CONCLUSIONS Anti-CASPR2 antibody-associated encephalitis has been rarely reported in children. It has a complex clinical presentation and a low incidence of tumor. Most pediatric patients have a favorable prognosis and relapse is uncommon.
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Affiliation(s)
- Qingyang Dou
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatrics, Guizhou Provincial People's Hospital, Guiyang, China
| | - Renke Li
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaomei Shu
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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40
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Liu P, Bai M, Ma C, Yan Y, Zhang G, Wu S, Li Z, Zhao D, Ren K, Li H, Guo J. Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis. Front Immunol 2021; 12:772763. [PMID: 34858431 PMCID: PMC8631873 DOI: 10.3389/fimmu.2021.772763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/25/2021] [Indexed: 11/13/2022] Open
Abstract
Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.
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Affiliation(s)
- Pei Liu
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China.,Department of Neurology, The First Hospital of Xi'an, Xi'an, China
| | - Miao Bai
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Chao Ma
- Department of Cardiology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yaping Yan
- College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Gejuan Zhang
- Department of Neurology, Xi'an No.3 Hospital, Xi'an, China
| | - Songdi Wu
- Department of Neurology, The First Hospital of Xi'an, Xi'an, China
| | - Zunbo Li
- Department of Neurology, Xi'an Gaoxin Hospital, Xi'an Medical College, Xi'an, China
| | - Daidi Zhao
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Kaixi Ren
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Hongzeng Li
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Jun Guo
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China
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41
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Franco G, Lazzeri G, Di Fonzo A. Parkinsonism and ataxia. J Neurol Sci 2021; 433:120020. [PMID: 34711421 DOI: 10.1016/j.jns.2021.120020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/09/2021] [Accepted: 09/29/2021] [Indexed: 11/17/2022]
Abstract
Ataxia is not a common feature in Parkinson's disease. Nevertheless, some rare forms of parkinsonism have ataxia as one of the main features in their clinical picture, especially those with juvenile or early-onset. On the other side, in cerebellar degenerative diseases, parkinsonism might accompany the typical symptoms and even become predominant in some cases. Many disorders involving different neurological systems present with a movement phenomenology reflecting the underlying pattern of pathological involvement, such as neurodegeneration with brain iron accumulation, neurodegeneration associated with calcium deposition, and metabolic and mitochondrial disorders. The prototype of sporadic disorders that present with a constellation of symptoms due to the involvement of multiple Central Nervous System regions is multiple system atrophy, whose motor symptoms at onset can be cerebellar ataxia or parkinsonism. Clinical syndromes encompassing both parkinsonian and cerebellar features might represent a diagnostic challenge for neurologists. Recognizing acquired and potentially treatable causes responsible for complex movement disorders is of paramount importance, since an early diagnosis is essential to prevent permanent consequences. The present review aims to provide a pragmatic overview of the most common diseases characterized by the coexistence of cerebellar and parkinsonism features and suggests a possible diagnostic approach for both inherited and sporadic disorders. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
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Affiliation(s)
- Giulia Franco
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy
| | - Giulia Lazzeri
- Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Alessio Di Fonzo
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy.
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Abstract
PURPOSE OF REVIEW To provide an update on recent developments regarding acquired, antibody-mediated, neuromuscular hyperexcitability syndromes, including Isaac's and Morvan's syndromes, cramp-fasciculation syndrome and rippling muscle disease, and their genetic differential diagnoses. RECENT FINDINGS Antibodies in auto-immune peripheral nerve hyperexcitability syndromes (PNHS) are directed against CASPR2 and LGI1, proteins of the voltage-gated potassium channel (VGKC) complex. We discuss the significance of 'double-negative' VGKC antibodies in PNHS and the rationale for ceasing VGKC antibody testing (but testing CASPR2 and LGI1 antibodies instead) in clinical practice. Recent case reports also expand the possible clinical phenotypes related to CASPR2/LGI1 antibodies, but the interpretation of these findings is complicated by the frequent association of antibody-mediated neuromuscular hyperexcitability syndromes with other auto-immune disorders (e.g. myasthenia gravis).Finally, a hereditary origin of neuromuscular hyperexcitability should always be considered, even in non-VGKC-related genes, as evidenced by the recently discovered high frequency of HINT1 mutations in people of Slavic origin. SUMMARY This review provides an update on recent clinical, immunological and genetic developments in neuromuscular hyperexcitability syndromes. We also provide a guide for the clinician for diagnosing and managing these disorders in clinical practice, with a special focus on the main differential diagnoses.
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Garza M, Piquet AL. Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia. Front Neurol 2021; 12:683048. [PMID: 34489848 PMCID: PMC8416494 DOI: 10.3389/fneur.2021.683048] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 07/28/2021] [Indexed: 12/29/2022] Open
Abstract
Movement disorders are a common feature of many antibody-associated neurological disorders. In fact, cerebellar ataxia is one of the most common manifestations of autoimmune neurological diseases. Some of the first autoantibodies identified against antigen targets include anti-neuronal nuclear antibody type 1 (ANNA-1 or anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1) also known as anti-Yo have been identified in paraneoplastic cerebellar degeneration. Historically these antibodies have been associated with an underlying malignancy; however, recently discovered antibodies can occur in the absence of cancer as well, resulting in the clinical syndrome of autoimmune cerebellar ataxia. The pace of discovery of new antibodies associated with autoimmune or paraneoplastic cerebellar ataxia has increased rapidly over the last few years, and pathogenesis and potential treatment options remains to be explored. Here we will review the literature on recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia including adaptor protein-3B2 (AP3B2); inositol 1,4,5-trisphophate receptor type 1 (ITPR1); tripartite motif-containing (TRIM) proteins 9, 67, and 46; neurochondrin; neuronal intermediate filament light chain (NIF); septin 5; metabotropic glutamate receptor 2 (mGluR2); seizure-related 6 homolog like 2 (SEZ6L2) and homer-3 antibodies. We will review their clinical characteristics, imaging and CSF findings and treatment response. In addition, we will discuss two clinical case examples of autoimmune cerebellar ataxia.
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Affiliation(s)
- Madeline Garza
- Department of Neurology, University of Colorado, Aurora, CO, United States
| | - Amanda L Piquet
- Department of Neurology, University of Colorado, Aurora, CO, United States
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44
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Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update. Brain Sci 2021; 11:brainsci11081035. [PMID: 34439654 PMCID: PMC8392118 DOI: 10.3390/brainsci11081035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/26/2021] [Accepted: 08/02/2021] [Indexed: 01/17/2023] Open
Abstract
The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.
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45
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Qin X, Yang H, Zhu F, Wang Q, Shan W. Clinical Character of CASPR2 Autoimmune Encephalitis: A Multiple Center Retrospective Study. Front Immunol 2021; 12:652864. [PMID: 34054814 PMCID: PMC8159154 DOI: 10.3389/fimmu.2021.652864] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/23/2021] [Indexed: 12/17/2022] Open
Abstract
Objective To examine the clinical characteristics of autoimmune encephalitis associated with the contactin-associated protein-2 (CASPR2) antibody. Materials and Methods Medical records of all patients diagnosed with CASPR2 antibody-associated encephalitis were retrospectively analysed. Data regarding demographic features, neurological symptoms and signs, laboratory tests, imaging results, treatments, and prognosis were collected. Results A total of 25 patients aged from 3 to 79 years old were enrolled in this study, with a median age of 43. Eight of 25 (32%) were female, and 17 of 25 (68%) were male. The median age of symptom onset was 42 years old with the course of disease from onset to hospital admission ranging from 2 days to 6 months (median was 17 days). Six patients (6/25) had fever as an onset symptom. During the course of disease, cognitive disturbance was the most common symptom, which was observed in 17 patients (17/25) in total. Eight patients (8/25) met the criteria for limbic encephalitis. Epileptic seizure occurred in six of these eight patients. Four patients (4/25) were diagnosed as Morvan syndrome. All patients were positive for anti-CASPR2 antibody in the serum (1:10-1:300). In six patients, antibodies were detected both in the blood and CSF (1:32-1:100). White blood cell (WBC) counts in the CSF were elevated in eight patients (8/25). The concentration of proteins in CSF increased in 10 patients (ranging from 480 to 1,337.6 mg/dl), decreased in seven patients (ranging from 23.2 to 130.5 mg/dl) and remained at a normal range in the other eight patients (ranging from 150 to 450 mg/dl). Abnormal electroencephalogram (EEG) activities included slow background activity and epileptic patterns. Abnormal signals in the bilateral hippocampus were detected by magnetic resonance imaging (MRI) in three patients presenting cognitive disturbance. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT. Eleven of 15 patients receiving immunotherapy experienced varying degrees of improvement. Relapse occurred in four of 25 patients (4/25) after 2 months. Conclusion CASPR-antibody-mediated autoimmune encephalitis is characterized by diverse clinical manifestations. The most prominent conclusion revealed by this retrospective analysis is the involvement of both central and peripheral nerve systems, as well as a lower relapse rate, a good response to immunotherapy, and favorable short-term prognosis after treatment was also demonstrated. Besides, additional work is necessary to evaluate the long-term prognosis.
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Affiliation(s)
- Xiaoxiao Qin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Huajun Yang
- Neurology Department, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fei Zhu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Beijing, China
| | - Qun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Beijing, China
| | - Wei Shan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Neuromodulation, Beijing, China
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46
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Shivaram S, Nagappa M, Seshagiri DV, Mahadevan A, Gangadhar Y, Sathyaprabha TN, Kumavat V, Bharath RD, Sinha S, Taly AB. Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease. Ann Indian Acad Neurol 2021; 24:178-185. [PMID: 34220060 PMCID: PMC8232480 DOI: 10.4103/aian.aian_574_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 06/29/2020] [Accepted: 09/07/2020] [Indexed: 11/13/2022] Open
Abstract
Background: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. Aims: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. Methods: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. Results: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. Conclusion: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.
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Affiliation(s)
- Sumanth Shivaram
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Madhu Nagappa
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Doniparthi V Seshagiri
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Anita Mahadevan
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Yashwanth Gangadhar
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - T N Sathyaprabha
- Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Vijay Kumavat
- Department of Transfusion Medicine and Hematology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Rose D Bharath
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Sanjib Sinha
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
| | - Arun B Taly
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
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47
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Wang J, Qiu Z, Li D, Dong H, Hao J, Liu Z. Anti-contactin-associated protein-like 2 antibody-associated cerebellar ataxia: A case report and literature review. J Neuroimmunol 2021; 353:577515. [PMID: 33640718 DOI: 10.1016/j.jneuroim.2021.577515] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/31/2021] [Accepted: 02/01/2021] [Indexed: 11/19/2022]
Abstract
The spectrum of anti-contactin-associated protein-like 2 (CASPR2) antibody-associated disease is expanding and the involvement of cerebellum was reported in the past few years. We report a 45-year-old male with chronically progressive cerebellar ataxia. CASPR2 antibodies were detected in his serum and cerebellar atrophy was observed on MRI. His symptoms improved prominently with steroids and intravenous immunoglobulins. 23 cases with CASPR2 antibodies and cerebellar ataxia were identified from previous publications. Most of patients showed acute or subacute onset with other typical presentations of anti-CASPR2 antibody-associated disease, such as limbic encephalitis. Immunotherapy was effective in the majority of patients.
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Affiliation(s)
- Jingsi Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
| | - Zhandong Qiu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
| | - Dawei Li
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
| | - Huiqing Dong
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
| | - Junwei Hao
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
| | - Zheng Liu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
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48
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Devine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neurol Disord 2021; 14:1756286420985323. [PMID: 33796141 PMCID: PMC7970694 DOI: 10.1177/1756286420985323] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 12/11/2020] [Indexed: 12/17/2022] Open
Abstract
We provide an overview of the varied presentations of paraneoplastic neurological syndromes. We also review the onconeural antibodies and their particular oncological and neurological associations. Recognition of these syndromes and their oncological associations is crucial, as early diagnosis and management has been associated with better patient outcomes. Specific management strategies and prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information can help tailor treatment approaches. We provide an outline of the diagnostic evaluation and treatment of various paraneoplastic neurological disorders, presenting with central and/or peripheral nervous system involvement. We briefly discuss neurologic immune checkpoint inhibitor-related adverse events, which can occasionally present with paraneoplastic neurological syndrome phenotypes.
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Affiliation(s)
- Michelle F Devine
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Naga Kothapalli
- Department of Neurology, University of Pittsburgh Medical Center, Pittsburg, PA, USA
| | | | - Divyanshu Dubey
- Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905-0002, USA
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49
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CASPR2 antibody-related movement disorders: case series. J Neurol 2021; 268:1533-1535. [PMID: 33399967 DOI: 10.1007/s00415-020-10357-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 11/18/2020] [Accepted: 12/04/2020] [Indexed: 10/22/2022]
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50
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Devine MF, St Louis EK. Sleep Disturbances Associated with Neurological Autoimmunity. Neurotherapeutics 2021; 18:181-201. [PMID: 33786802 PMCID: PMC8116412 DOI: 10.1007/s13311-021-01020-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2021] [Indexed: 12/29/2022] Open
Abstract
Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5; leucine-rich, glioma-inactivated protein 1 (LGI1); contactin-associated protein 2 (CASPR2); N-methyl-D-aspartate (NMDA)-receptor; Ma2; dipeptidyl-peptidase-like protein-6 (DPPX); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R); anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu); anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri); gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R); metabotropic glutamate receptor 5 (mGluR5); and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.
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Affiliation(s)
- Michelle F Devine
- Mayo Clinic Center for Sleep Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
- Department of Medicine (Division of Pulmonary, Critical Care, and Sleep Medicine), Rochester, MN, USA.
- Department of Neurology, Mayo Clinic Health System Southwest Wisconsin-La Crosse, Mayo Clinic and Foundation, Rochester, MN, USA.
- Olmsted Medical Center, MN, Rochester, USA.
- Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
| | - Erik K St Louis
- Mayo Clinic Center for Sleep Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
- Mayo Sleep Behavior and Neurophysiology Research Laboratory, Rochester, MN, USA
- Department of Medicine (Division of Pulmonary, Critical Care, and Sleep Medicine), Rochester, MN, USA
- Department of Neurology, Mayo Clinic Health System Southwest Wisconsin-La Crosse, Mayo Clinic and Foundation, Rochester, MN, USA
- Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
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